Imrie A, Carr A, Duncombe C, Finlayson R, Vizzard J, Law M, Kaldor J, Penny R, Cooper D A
Centre for Immunology, St Vincent's Hospital, Sydney, Australia.
J Infect Dis. 1996 Jul;174(1):195-8. doi: 10.1093/infdis/174.1.195.
Human immunodeficiency virus type 1 (HIV-1) variants with reduced in vitro sensitivity to zidovudine, conferred by specific mutations in the viral reverse transcriptase, emerge during prolonged therapy. Late-stage disease and declining CD4 cell count are associated with more rapid emergence of these resistant variants. Isolates of HIV-1 from seroconverters were screened for the zidovudine-resistance marker mutation at codon 215. HIV-1 with the altered genotype was detected in 5 (8.2%) of 61 patients soon after onset of symptomatic primary illness and from the sex partner of 1 patient. These transmitted resistant viruses were either replaced by strains susceptible to zidovudine within a few months of infection or persisted for up to 1 year in the absence of prolonged zidovudine therapy. The resistant genotype persisted in 3 of 5 seroconverters but in 2 patients had reverted to wild type at 48 and 52 weeks. Primary infection with zidovudine-resistant variants of HIV-1 was not associated with a more severe symptomatic primary illness or more rapid CD4 cell decline at 1 year after infection.
在长期治疗过程中,会出现因病毒逆转录酶的特定突变而导致对齐多夫定体外敏感性降低的1型人类免疫缺陷病毒(HIV-1)变异株。晚期疾病和CD4细胞计数下降与这些耐药变异株的更快出现有关。对血清转化者的HIV-1分离株进行了第215密码子齐多夫定耐药标记突变的筛查。在61例患者出现有症状的原发性疾病后不久,有5例(8.2%)检测到基因型改变的HIV-1,其中1例来自患者的性伴侣。这些传播的耐药病毒在感染后的几个月内要么被对齐多夫定敏感的毒株取代,要么在没有长期齐多夫定治疗的情况下持续长达1年。5例血清转化者中有3例的耐药基因型持续存在,但有2例患者在48周和52周时已恢复为野生型。感染HIV-1的齐多夫定耐药变异株的原发性感染与感染后1年更严重的有症状原发性疾病或更快的CD4细胞下降无关。